Endoparasite control agent

ABSTRACT

The present invention is intended to provide a novel parasiticide, antiprotozoal or other endoparasite control agents which are effective for controlling animal endoparasites that have been impossible to control by conventional ones. Provided is an endoparasite control agent comprising, as an active ingredient, a carboxamide derivative represented by the general formula (I): 
     
       
         
         
             
             
         
       
     
     or a salt thereof.

FIELD

The present invention relates an endoparasite control agent comprising acarboxamide derivative or a salt thereof as an active ingredient,, and amethod for controlling endoparasites, comprising orally or parenterallyadministering the endoparasite control agent.

BACKGROUND ART

Certain kinds of carboxamide derivatives have been known to havemicrobicidal activity (see Patent Literature 1 to 12). However, theliterature does not describe that these compounds are effective for thedisinfection or control of endoparasites in animals such as mammals andbirds. It is also known that certain kinds of carboxamide derivativesare effective against nematodes that may damage agricultural products(see Patent Literature 4 or 5), but there is no specific disclosure asto whether these compounds are effective against endoparasites inanimals. Furthermore, there is a report that compounds that inhibitsuccinate-ubiquinone reductase (mitochondrial complex II), which is oneof the respiratory enzymes of endoparasites, can serve as anendoparasite control agent (see Non Patent Literature 1).

In addition, Patent Literature 13 discloses certain kinds of carboxamidederivatives which are effective against endoparasites. However, there isno disclosure of the effects of the compounds of the present inventionagainst endoparasites.

Generally, parasitosis is caused by infestation of host animals withparasites such as unicellular protists (protozoa), multicellularhelminths and arthropods. It is reported that the incidence ofparasitosis in Japan has been remarkably decreased by improvement ofenvironmental hygiene, but on a global scale, particularly in developingcountries, parasitosis still widely prevails and causes tremendousdamage. In recent years, there have been seen the introduction ofinfection sources via long- or short-term travelers having visited suchcountries; parasitic infection due to the consumption of food imports orraw meat and fish meat, which have become more available thanks to theadvance in freezing and logistics technologies; and the transmission ofparasitosis from pets. Under such circumstances, the incidence ofparasitosis is on an upward trend again. Another problem is thatimmunodeficiency caused by mass administration of immunosuppressants,anticancer drugs, etc. or by AIDS etc. allows usually non-pathogenic orlow-pathogenic parasites to express their pathogenicity and to causeopportunistic infection in hosts. Further, parasitosis in domesticanimals, such as pigs, horses, cattle, sheep, dogs, cats and domesticfowls, is a universal and serious economic problem. That is, parasiticinfection of domestic animals causes anemia, malnutrition, debility,weight loss, and serious damage of intestinal tract walls, tissues andorgans, and may result in decline in feed efficiency and productivity,leading to a great economic loss. Therefore, novel parasiticides,antiprotozoals or other endoparasite control agents have always beendesired.

CITATION LIST Patent Literature

Patent Literature 1: JP-A 01-151546

Patent Literature 2: WO 2007/060162

Patent Literature 3: JP-A 53-9739

Patent Literature 4: WO 2007/108483

Patent Literature 5: WO 2007/104496

Patent Literature 6: WO 2008/101975

Patent Literature 7: WO 2008/101976

Patent Literature 8: WO 2008/003745

Patent Literature 9: WO 2008/003746

Patent Literature 10: WO 2009/012998

Patent Literature 11: WO 2009/127718

Patent Literature 12: WO 2010/106971

Patent Literature 13: WO 2012/118139

Non Patent Literature

Non Patent Literature 1: Kiyoshi Kita, “Kansen (Infection)”, Winter2010, Vol. 40-4, 310-319

SUMMARY OF INVENTION Technical Problem

In view of the above-described circumstances, the present invention ismainly intended to provide a novel parasiticide, antiprotozoal or otherendoparasite control agents which are effective for controlling animalendoparasites that have been impossible to control by conventional ones.

Solution to Problem

The present inventors conducted extensive research to solve theabove-described problems. As a result, the present inventors found thata carboxamide derivative represented by the general formula (I) of thepresent invention and a salt thereof are highly effective forcontrolling endoparasites. The present inventors further conducted agreat deal of examination and then completed the present invention. Thatis, the present invention relates to the following.

[1] An endoparasite control agent comprising, as an active ingredient, acarboxamide derivative represented by the general formula (I):

wherein

A represents a nitrogen atom or a C—Y⁵ group (wherein Y⁵ is a hydrogenatom or a (C₁-C₆) alkyl group),

X¹ and X² may be the same or different, and each represent

-   (a1) a hydrogen atom;-   (a2) a halogen atom;-   (a3) a (C₁-C₆) alkyl group;-   (a4) a halo (C₁-C₆) alkyl group;-   (a5) a (C₁-C₆ alkoxy group; or-   (a6) a halo (C₁-C₆) alkoxy group,

R¹ and R² may be the same or different, and are selected from the groupconsisting of

-   (b1) a hydrogen atom;-   (b2) a halogen atorn;-   (b3) a (C₁-C₆) alkyi group;-   (b4) a (C₁-C₆) alkoxy group; and-   (b5) a halo (C₁-C₆) alkyl group, or optionally-   (b6) R¹ and R² together with the carbon atom bound to R¹ and R² form    a (C₃-C₆) cycloalkane,

R³ and R⁴ may be the same or different, and are selected from the groupconsisting of

-   (c1) a hydrogen atom;-   (c2) a halogen atom;-   (c3) a (C₁-C₆) alkyl group;-   (c4) a (C₁-C₆) alkoxy group; and-   (c5) a halo (C₁-C₆) alkyl group; or optionally-   (c6) R³ and R⁴ together with the carbon atom bound to R³ and R⁴ form    a (C₃-C₆) cycloalkane,

Y¹ represents

-   (d1) a hydrogen atom;-   (d2) a halogen atom;-   (d3) a (C₁-C₆) alkyl group;-   (d4) a halo C₁-C₆) alky group;-   (d5) a (C₁-C₆) alkoxy group; or-   (d6) a halo (C₁-C₆) alkoxy group,

Y² and Y⁴ may be the same or different, and each represent

-   (e1) a hydrogen atom;-   (e2) a halogen atom;-   (e3) a (C₁-C₆) alkyl group;-   (e4) a halo (C₁-C₆) alkyl group;-   (e5) a (C₁-C₆) alkoxy group; or-   (e6) a halo (C₁-C₆) alkoxy group, and

Y³ represents

-   (f1) a phenyl group;-   (f2) a phenyl group having, on the ring, 1 to 5 substituting groups    which may be the same or different and are selected from the group    consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro    group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f3) a phenoxy group;-   (f4) a phenoxy group having, on the ring, 1 to 5 substituting groups    which may be the same or different and are selected from the group    consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro    group, (d) a (C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g)    a halo (C₁-C₆) alkoxy group;-   (f5) a pyridyl group;-   (f6) a pyridyl group having, on the ring, 1 to 4 substituting groups    which may be the same or different and are selected from the group    consisting of (a) a halogen atom, a cyano group, (c) a nitro    group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f7) a pyridyloxy group;-   (f8) a pyridyloxy group having, on the ring, 1 to 4 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f9) a pyrimidyloxy group;-   (f10) a pyrimidyloxy group having, on the ring, 1 to 3 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f11) a pyrazyloxy group;-   (f12) a pyrazyloxy group having, on the ring, 1 to 3 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f13) a pyrazolyloxy group;-   (f14) a pyrazolyloxy group having, on the ring, 1 to 3 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group, (g) a halo (C₁-C₆) alkoxy group    and (h) a formyl group;-   (f15) a quinolyloxy group;-   (f16) a quinolyloxy group having, on the ring, 1 to 6 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f17) a quinoxalyloxy group;-   (f18) a quinoxalyloxy group having, on the ring, 1 to 5 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f19) a benzoxazolyloxy group;-   (f20) a benzoxazolyloxy group having, on the ring, 1 to 4    substituting groups which may be the same or different and are    selected from the group consisting of (a) a halogen atom, (b) a    cyano group, (c) a nitro group, (d) a (C₁-C₆) alkyl group, (e) a    halo (C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g) a halo    (C₁-C₆) alkoxyl group;-   (f21) a benzothiazolyloxy group; or-   (f22) a benzothiazolyloxy group having, on the ring, 1 to 4    substituting groups which may be the same or different and are    selected from the group consisting of (a) a halogen atom, (b) a    cyano group, (c) a nitro group, (d) a (C₁-C₆) alkyl group, (e) a    halo (C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g) a halo    (C₁-C₆) alkoxy group, or a salt thereof.

[2] The endoparasite control agent according to the above [1], wherein

A represents a nitrogen atom or a C—H group,

X¹ and X² may be the same or different, and each represent

-   (a1) a hydrogen atom;-   (a2) a halogen atom; or-   (a4) a halo (C₁-C₆) alkyl group,

R¹ and R² each represent (b1) a hydrogen atom,

-   R³ and R⁴ may be the same or different, and are selected from the    group consisting of-   (c1) a hydrogen atom;-   (c3) a (C₁-C₆) alkyl group; and-   (c4) a (C₁-C₆) alkoxy group, or optionally-   (c6) R³ and R⁴ together with the carbon atom bound to R³ and R⁴ form    a (C₁-C₆) cycloalkane,

Y¹ represents (d2) a halogen atom,

Y² and Y⁴ each represent (e1) a hydrogen atom, and

Y³ is selected from the group consisting of

-   (f1) a phenyl group;-   (f2) a phenyl group having, on the ring, 1 to 5 substituting groups    which may be the same or different and are selected from the group    consisting of a) a halogen atom, (b) a cyano group, (c) a nitro    group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    groups, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f3) a phenoxy group;-   (f4) a phenoxy group having, on the ring, 1 to 5 substituting groups    which may be the same or different and are selected from the group    consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro    group, (d) a (C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g)    a halo (C₁-C₆) alkoxy group;-   (f5) a pyridyl group;-   (f7) a pyridyloxy group;

(f8) a pyridyloxy group having, on the ring, 1 to 4 substituting groupswhich may be the same or different and are selected from the groupconsisting of (a) a halogen atom, (b) a cyano group, (c) a nitro group,(d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl group, (f) a (C₁-C₆)alkoxy group and (g) a halo (C₁-C₆) alkoxy group;

-   (f10) a pyrimidyloxy group having, on the ring, 1 to 3 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f11) a pyrazyloxy group;-   (f12) a pyrazyloxy group having, on the ring, 1 to 3 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f14) a pyrazolyloxy group having, on the ring, 1 to 3substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group, (g) a halo (C₁-C₆) alkoxy group    and (h) a formyl group;-   (f15) a quinolyloxy group;-   (f17) a quinoxalyloxy group;-   (f19) a benzoxazolyloxy group;-   (f21) a benzothiazolyloxy group; and-   (f22) a benzothiazolyloxy group having, on the ring, 1 to 4    substituting groups which may be the same or different and are    selected from the group consisting of (a) a halogen atom, (b) a    cyano group, (c) a nitro group, (d) a (C₁-C₆) alkyl group, (e) a    halo (C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g) a halo    (C₁-C₆) alkoxy group.

[3] The endoparasite control agent according to the above [1], wherein

A represents a C—H group,

X¹ and X² may be the same or different, and are selected from the groupconsisting of

-   (a1) a hydrogen atom;-   (a2) a halogen atom; and-   (a4) a halo (C₁-C₆) alkyl group,

R¹ and R² each represent (b1) a hydrogen atom,

R³ and R⁴ may be the same or different, and are selected from the groupconsisting of

-   (c1) a hydrogen atom;-   (c3) a (C₁-C₆) alkyl group; and-   (c4) a (C₁-C₆) alkoxy group, or optionally-   (c6) R³ and R⁴ together with the carbon atom bound to R³ and R⁴ form    a (C₃-C₆) cycloalkane,

Y¹ represents (d2) a halogen atom,

Y² and Y⁴ each represent (e1) a hydrogen atom, and

-   Y³ is selected from the group consisting of-   (f1) a phenyl group;-   (f2) a phenyl group having, on the ring, 1 to 5 substituting groups    which may be the same or different and are selected from the group    consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro    group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f3) a phenoxy group;-   (f4) a phenoxy group having, on the ring, 1 to 5 substituting groups    which may be the same or different and are selected from the group    consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro    group, (d) a (C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g)    a halo (C₁-C₆) alkoxy group;-   (f5) a pyridyl group;-   (f7) a pyridyloxy group;-   (f8) a pyridyloxy group having, on the ring, 1 to 4 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f10) a pyrimidyloxy group having, on the ring, 1 to 3 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f11) a pyrazyloxy group;-   (f12) a pyrazyloxy group having, on the ring, 1 to 3 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁ 1-C₆) alkoxy    group;-   (f14) a pyrazolyloxy group having, on the ring, 1 to 3 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆C) alkoxy group, (g) a halo (C₁-C₆) alkoxy group    and (h) a formyl group;-   (f15) a quinolyloxy group;-   (f17) a quinoxalyloxy group;-   (f19) a benzoxazolyloxy group;-   (f21) a benzothiazolyloxy group; and-   (f22) a benzothiazolyloxy group having, on the ring, 1 to 4    substituting groups which may be the same or different and are    selected from the group consisting of (a) a halogen atom, (b) a    cyano group, (c) a nitro group, (d) a (C₁-C₆) alkyl group, (e) a    halo (C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g) a halo    (C₁-C₆) alkoxy group.

[4] The endoparasite control agent according to the above [1], wherein

A represents a nitrogen atom,

X¹ and X² may be the same or different, and are selected from the groupconsisting of

-   (a1) a hydrogen atom;-   (a2) a halogen atom; and-   (a4) a halo (C₁-C₆) alkyl group,

R¹ and R² each represent (b1) a hydrogen atom,

-   R³ and R⁴ may be the same or different, and are selected from the    group consisting of-   (c1) a hydrogen atom; and-   (c3) a (C₁-C₆) alkyl group,

Y¹ represents

-   (d2) a halogen atom; or-   (d3) a (C₁-C₆) alkyl group,

Y² and Y⁴ each represent (e1) a hydrogen atom, and

Y³ is selected from the group consisting of

-   (f1) a phenyl group;-   (f2) a phenyl group having, on the ring, 1 to 5 substituting groups    which may be the same or different and are selected from the group    consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro    group, (d) a (C₁-C₆) alkyl group, (f) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f3) a phenoxy group;-   (f4) a phenoxy group having, on the ring, 1 to 5 substituting groups    which may be the same or different and are selected from the group    consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro    group, (d) a (C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g)    a halo (C₁-C₆) alkoxy group; and-   (f5) a pyridyl group.

[5] A method for controlling endoparasites, comprising orally orparenterally administering an effective amount of the endoparasitecontrol agent according to any one of the above [1] to [4] to anon-human mammal or a bird.

[6] A method for controlling endoparasites, comprising orally orparenterally administering an effective amount of the endoparasitecontrol agent according to any one of the above [1] to [4] to anon-human mammal.

[7] The method according to the above [5]; or [6], wherein the non-humanmammal is a domestic animal.

[8] A method for controlling endoparasites, comprising orally orparenterally administering an effective amount of the endoparasitecontrol agent according to any one of the above [1] to [4] to a human.

[9] The carboxamide derivative specified in any one of the above [1] to[4] or a salt thereof for use in control of endoparasites.

[10] Use of the carboxamide derivative specified in any one of the above[1] to [4] or a salt thereof for production of endoparasite controlagents.

[11] Use of the carboxamide derivative specified in any one of the above[1] to [4] or a salt thereof for control of endoparasites.

Advantageous Effects of Invention

The present invention provides an endoparasite control agent havingbetter performance in the disinfection or control of endoparasites ascompared with the conventional art.

DESCRIPTION OF EMBODIMENTS

The definitions in connection with the general formula (I) representingthe carboxamide derivative of the present invention are described below.

The “halogen atom” refers to a chlorine atom, a bromine atom, an iodineatom or a fluorine atom.

The “(C₁-C₆) alkyl group” refers to a straight-chain or branched-chainalkyl group of 1 to 6 carbon atoms, for example, a methyl group, anethyl group, a n-propyl group, an isopropyl group, a n-butyl group, anisobutyl group, a sec-butyl group, a tert-butyl group, a n-pentyl group,a neopentyl group, a n-hexyl group or the like.

The “(C₁-C₆) alkoxy group” refers to a straight-chain or branched-chainalkoxy group of 1 to 6 carbon atoms, for example, a methoxy group, anethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group,a sec-butoxy group, a tert-butoxy group, a n-pentyloxy group, anisopentyloxy group, a neopentyloxy group, a n-hexyloxy group or thelike.

The “halo (C₁-C₆) alkyl group” refers to a straight-chain orbranched-chain alkyl group of 1 to 6 carbon atoms substituted with oneor more halogen atoms which may be the same or different from eachother, for example, a trifluoromethyl group, a difluoromethyl group, aperfluoroethyl group, a hexafluoroisopropyl group, a perfluoroisopropylgroup, a chloromethyl group, a bromomethyl group, a 1-bromoethyl group,a 2,3-dibromopropyl group or the like.

The “halo (C₁-C₆) alkoxy group” refers to a straight-chain orbranched-chain alkoxy group of 1 to 6 carbon atoms substituted with oneor more halogen atoms which may be the same or different from eachother, for example, a trifluoromethoxy group, a difluoromethoxy group, aperfluoroethoxy group, a perfluoroisopropoxy group, a chloromethoxygroup, a bromomethoxy group, a 1-bromoethoxy group, a 2,3-dibromopropoxygroup or the like.

The “(C₃-C₆) cycloalkane” formed of R¹ and R² together with the carbonatom bound to R¹ and R² is, for example, cyclopropane, cyclobutane,cyclopentane, cyclohexane or the like.

The “(C₃-C₆) cycloalkane” formed of R³ and R⁴ together with the carbonatom bound to R³ and R⁴ is, for example, cyclopropane, cyclobutane,cyclopentane, cyclohexane or the like.

Examples of the salt of the carboxamide derivative represented by thegeneral formula (I) of the present invention include inorganic acidsalts, such as hydrochlorides, sulfates, nitrates and phosphates;organic acid salts, such as acetates, fumarates, maleates, oxalates,methanesulfonates, benzenesulfonates and p-toluenesulfonates; and saltswith an inorganic or organic base such as a sodium ion, a potassium ion,a calcium ion and a trimethylammonium ion.

As the carboxamide derivative of the present invention, preferred is acompound of the general formula (I) in which

A represents a nitrogen atom or a C—H group,

X¹ and X² may be the same or different, and each represent

-   (a1) a hydrogen atom;-   (a2) a halogen atom; or-   (a4) a halo (C₁-C₆) alkyl group,

R¹ and R² each represent (b1) a hydrogen atom,

R³ and R⁴ may be the same or different, and are selected from the groupconsisting of

-   (c1) a hydrogen atom;-   (c3) a (C₁-C₆) alkyl group; and-   (c4) a (C₁-C₆) alkoxy group, or optionally-   (c6) R³ and R⁴ together with the carbon atom bound to R³ and R⁴ form    a (C₃-C₆) cycloalkane,

Y¹ represents (d2) a halogen atom,

Y² and Y⁴ each represent (e1) a hydrogen atom, and

Y³ is selected from the group consisting of

-   (f1) a phenyl group;-   (f2) a phenyl group having, on the ring, 1 to 5 substituting groups    which may be the same or different and are selected from the group    consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro    group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f3) a phenoxy group;-   (f4) a phenoxy group having, on the ring, 1 to 5 substituting groups    which may be the same or different and are selected from the group    consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro    group, (d) a (C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g)    a halo (C₁-C₆) alkoxy group;-   (f5) a pryidyl group;-   (f7) a pyridyloxy group;-   (f8) a pyridyloxy group having, on the ring, 1 to 4 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f10) a pyrimidyloxy group having, on the ring, 1 to 3 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆)alkoxy    group;-   (f11) a pyrazyloxy group;-   (f12) a pyrazyloxy group having, on the ring, 1 to 3 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f14) a pyrazolyloxy group having, on the ring, 1 to 3 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group, (g) a halo (C₁-C₆) alkoxy group    and (h) a formyl group;-   (f15) a quinolyloxy group;-   (f17) a quinoxalyloxy group;-   (f19) a benzoxazolyoxy group;-   (f21) a benzothiazolyloxy group; and-   (f22) a benzothiazolyloxy group having, on the ring, 1 to 4    substituting groups which may be the same or different and are    selected from the group consisting of (a) a halogen atom, (b) a    cyano group, (c) a nitro group, (d) a (C₁-C₆) alkyl group, (e) a    halo (C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g) a halo    (C₁-C₆) alkoxy group, or a salt thereof.

As the carboxamide derivative of the present invention, furtherpreferred is a compound of the general formula (I) in which

A represents a C—H group,

X¹ and X² may be the same or different, and are selected from the groupconsisting of

-   (a1) a hydrogen atom;-   (a2) a halogen atom; and-   (a4) a halo (C₁-C₆) alkyl group,

R¹ and R² each represent (b1) a hydrogen atom,

R³ and R⁴ may be the same or different, and are selected from the groupconsisting of

-   (c1) a hydrogen atom;-   (c3) a (C₁-C₆) alkyl group; and-   (c4) a (C₁-C₆) alkoxy group, or optionally-   (c6) R³ and R⁴ together with the carbon atom bound to R³ and R⁴ form    a (C₃-C₆) cycloalkane,

Y¹ represents (d2) a halogen atom,

Y² and Y⁴ each represent (e1) a hydrogen atom, and

Y³ is selected from the group consisting of

-   (f1) a phenyl group;-   (f2) a phenyl group having, on the ring, 1 to 5 substituting groups    which may be the same or different and are selected from the group    consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro    group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f3) a phenoxy group;-   (f4) a phenoxy group having, on the ring, 1 to 5 substituting groups    which may be the same or different and are selected from the group    consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro    group, (d) a (C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g)    a halo (C₁-C₆) alkoxy group;-   (f5) a pyridyl group;-   (f7) a pyridyloxy group;-   (f8) a pyridyloxy group having, on the ring, 1 to 4 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo ((C₁-C₆) alkoxy    group;-   (f10) a pyrimidyloxy group having, on the ring, 1 to 3 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆ alkoxy    group;-   (f11) a pyrazyloxy group;-   (f12) a pyrazyloxy group having, on the ring, 1 to 3 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (e14) a pyrazolyloxy group having, on the ring, 1 to 3 substituting    groups which may be the same or different and are selected from the    group consisting of (a) a halogen atom, (b) a cyano group, (c) a    nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group, (g) a halo (C₁-C₆) alkoxy group    and (h) a formyl group;-   (f15) a quinolyloxy group;-   (f17) a quinoxalyloxy group;-   (f19) a benzoxazolyloxy group;-   (f21) a benzothiazolyloxy group; and

(f22) a benzothiazolyloxy group having, on the ring, 1 to 4 substitutinggroups which may be the same or different and are selected from thegroup consisting of (a) a halogen atom, (b) a cyano group, (c) a nitrogroup, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl group, (f) a(C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy group, or a saltthereof.

Also preferred is a compound of the general formula (I) in which

A represents a nitrogen atom,

X¹ and X² may be the same or different, and are selected from the groupconsisting of

-   (a1) a hydrogen atom;-   (a2) a halogen atom; and-   (a4) a halo (C₁-C₆) alkyl group,

R¹ and R² each represent (b1) a hydrogen atom,

R³ and R⁴ may be the same or different, and are selected from the groupconsisting of

-   (c1) a hydrogen atom; and-   (c3) a (C₁-C₆) alkyl group,

Y¹ represents

-   (d2) a halogen atom; or-   (d3) a (C₁-C₆) alkyl group,

Y² and Y⁴ each represent (e1) a hydrogen atom, and

Y³ is selected from the group consisting of

-   (f1) a phenyl group;-   (f2) a phenyl group having, on the ring, 1 to 5 substituting groups    which may be the same or different and are selected from the group    consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro    group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl    group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy    group;-   (f3) a phenoxy group;-   (f4) a phenoxy group having, on the ring, 1 to 5 substituting groups    which may be the same or different and are selected from the group    consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro    group, (d) a (C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g)    a halo (C₁-C₆) alkoxy group; and-   (f5) a pyridyl group, or a salt thereof.

The compound represented by the general formula (I) of the presentinvention can be produced by any of the production methods described inJP-A 01-151546, WO 2007/060162, JP-A 53-9739, WO 2007/108483, WO2008/101975, WO 2008/101976, WO 2008/003745, WO 2008/003746, WO2009/012998, WO 2009/127718, WO 2010/106971 and WO 2012/113139, themethod described in Shin-Jikken Kagaku Kouza 14 (Maruzen, Dec. 20,1977), a modified method of the foregoing, or the like.

Representative examples of the carboxamide derivative represented by thegeneral formula (I) of the present invention are shown in tables 1 and2, but the present invention is not limited thereto. In Tables 1 and 2,“MeO” stands for a methoxy group, “Ph” stands for a phenyl group, “Py”stands for a pyridyl group, “PhO” stands for a phenoxy group, and “PyO”stands for a pyridyloxy group. Shown in the column of “Physicalproperty” are mass spectral data.

Q1 to Q19 represent the following structures. The black circle in eachof the formulae Q1 to Q19 represents a binding site.

TABLE 1 Compound Physical No. X¹ X² R³ R⁴ Y¹ Y³ property 1-1 CF₃ H H HCl Q3 489 (M + 1) 1-2 CF₃ H H H Cl Q4 535 (M + 1) 1-3 CF₃ H H H Cl Q5490 (M + 1) 1-4 CF₃ H H H Cl Q6 456 (M + 1) 1-5 CF₃ H H H Cl Q7 422(M + 1) 1-6 CF₃ H H H Cl Q8 482 (M + 1) 1-7 CF₃ H H H Cl Q9 450 (M + 1)1-8 CF₃ H H H Cl Q10 456 (M + 1) 1-9 CF₃ H H H Cl Q11 490 (M + 1) 1-10CF₃ H H H Cl Q12 470 (M + 1) 1-11 CF₃ H H H Cl Q13 470 (M + 1) 1-12 CF₃H H H Cl Q14 466 (M + 1) 1-13 CF₃ H H H Cl Q15 471 (M + 1) 1-14 CF₃ H HH Cl Q16 472 (M + 1) 1-15 CF₃ H H H Cl Q17 477 (M + 1) 1-16 CF₃ H H H ClQ18 511 (M + 1) 1-17 CF₃ H H H Cl Q19 461 (M + 1) 1-18 CF₃ H H H Cl PhO420 (M + 1) 1-19 CF₃ H H H Cl 4-CF₃—PhO 488 (M + 1) 1-20 I H H H Cl Q1581 (M + 1) 1-21 I H H H Cl Q2 547 (M + 1) 1-22 I H H H Cl Q3 547(M + 1) 1-23 I H H H Cl Q4 593 (M + 1) 1-24 I H H H Cl Q5 548 (M + 1)1-25 I H H H Cl Q6 514 (M + 1) 1-26 I H H H Cl Q7 480 (M + 1) 1-27 I H HH Cl Q8 540 (M + 1) 1-28 I H H H Cl Q9 508 (M + 1) 1-29 I H H H Cl Q10514 (M + 1) 1-30 I H H H Cl Q11 550 (M + 1) 1-31 I H H H Cl Q12 528(M + 1) 1-32 I H H H Cl Q13 528 (M + 1) 1-33 I H H H Cl Q14 524 (M + 1)1-34 I H H H Cl Q15 529 (M + 1) 1-35 I H H H Cl Q16 530 (M + 1) 1-36 I HH H Cl Q17 535 (M + 1) 1-37 I H H H Cl Q18 569 (M + 1) 1-38 I H H H ClQ19 519 (M + 1) 1-39 I H H H Cl PhO 478 (M + 1) 1-40 I H H H Cl4-CF₃—PhO 546 (M + 1) 1-41 CF₃ H Me H Cl Q1 537 (M + 1) 1-42 CF₃ H Me HCl Q2 503 (M + 1) 1-43 CF₃ H Me H Cl Q3 503 (M + 1) 1-44 CF₃ H Me Me ClQ1 551 (M + 1) 1-45 CF₃ H Me Me Cl Q2 517 (M + 1) 1-46 CF₃ H Me Me Cl Q3517 (M + 1) 1-47 CF₃ H CH₂CH₂ Cl Q1 549 (M + 1) 1-48 CF₃ H CH₂CH₂ Cl Q2515 (M + 1) 1-49 CF₃ H CH₂CH₂ Cl Q3 515 (M + 1) 1-50 CF₃ H H H Cl4-CF₃—Ph 472 (M + 1) 1-51 CF₃ H H H Cl 3-CF₃—Ph 472 (M + 1) 1-52 CF₃ H HH Cl 3,5-F₂—Ph 440 (M + 1) 1-53 CF₃ H H H Cl 4-MeO—Ph 434 (M + 1) 1-54CF₃ H H H Cl Ph 404 (M + 1) 1-55 CF₃ H H H Cl 4-Py 405 (M + 1) 1-56 CF₃H H H Cl 3-Py 405 (M + 1) 1-57 CF₃ H Me H Cl 4-CF₃—Ph 486 (M + 1) 1-58CF₃ H Me H Cl Ph 418 (M + 1) 1-59 CF₃ H Me H Cl 4-Py 419 (M + 1) 1-60CF₃ H MeO H Cl Q1 553 (M + 1) 1-61 CF₃ H MeO H Cl Q2 519 (M + 1) 1-62CF₃ H MeO H Cl Q3 521 (M + 1) 1-63 CF₃ H MeO H Cl Q17 507 (M + 1) 1-64CF₃ H MeO H Cl PhO 418 (−MeOH) 1-65 CF₃ H MeO H Cl 4-CF₃—PhO 518 (M + 1)1-66 CF₃ H MeO H Cl 4-MeO—Ph 448 (−MeOH) 1-67 CF₃ H MeO H Cl 3-PyO 451(M + 1) 1-68 F F Me H Cl Q1 505 (M + 1) 1-69 F F Me H Cl Q2 471 (M + 1)1-70 F F Me H Cl Q3 471 (M + 1) 1-71 F F Me Me Cl Q1 519 (M + 1) 1-72 FF Me Me Cl Q2 485 (M + 1) 1-73 F F Me Me Cl Q3 485 (M + 1) 1-74 F FCH₂CH₂ Cl Q3 517 (M + 1) 1-75 F F CH₂CH₂ Cl Q2 483 (M + 1) 1-76 F FCH₂CH₂ Cl Q3 483 (M + 1) 1-77 CF₃ H Me Me Me Q1 531 (M + 1) 1-78 CF₃ HMe Me Me Q2 497 (M + 1) 1-79 I H Me Me Me Q1 589 (M + 1) 1-80 F F Me MeMe Q1 499 (M + 1) In Table 1, R¹, R², Y² and Y⁴ represent H, and Arepresents CH.

TABLE 2 Compound Physical No. X¹ R³ R⁴ Y¹ Y³ property 2-1 CF₃ H H Cl Ph405 (M + 1) 2-2 CF₃ H H Cl 4-CF₃—Ph 473 (M + 1) 2-3 CF₃ H H Cl 3-CF₃—Ph473 (M + 1) 2-4 CF₃ H H Cl 3,5-F₂—Ph 441 (M + 1) 2-5 CF₃ H H Cl 4-MeO—Ph435 (M + 1) 2-6 CF₃ H H Cl 4-Py 406 (M + 1) 2-7 CF₃ H H Cl 3-Py 406(M + 1) 2-8 CF₃ Me H Cl Ph 419 (M + 1) 2-9 CF₃ Me H Cl 4-CF₃—Ph 487(M + 1) 2-10 CF₃ Me H Cl 3-CF₃—Ph 487 (M + 1) 2-11 CF₃ Me H Cl 3,5-F₂—Ph455 (M + 1) 2-12 CF₃ Me Me Cl Ph 433 (M + 1) 2-13 CF₃ Me Me Cl 4-CF₃—Ph501 (M + 1) 2-14 CF₃ Me Me Cl 3-CF₃—Ph 501 (M + 1) 2-15 CF₃ Me Me Cl3,5-F₂—Ph 469 (M + 1) 2-16 I H H Cl Ph 463 (M + 1) 2-17 I H H Cl4-CF₃—Ph 531 (M + 1) 2-18 I H H Cl 3-CF₃—Ph 531 (M + 1) 2-19 I H H Cl3,5-F₂—Ph 499 (M + 1) 2-20 I H H Cl 4-MeO—Ph 493 (M + 1) 2-21 I H H Cl4-Py 464 (M + 1) 2-22 I H H Cl 3-Py 464 (M + 1) 2-23 I Me H Cl Ph 477(M + 1) 2-24 I Me H Cl 4-CF₃—Ph 2-25 I Me H Cl 3-CF₃—Ph 2-26 I Me H Cl3,5-F₂—Ph 2-27 I Me Me Cl Ph 2-28 I Me Me Cl 4-CF₃—Ph 2-29 I Me Me Cl3-CF₃—Ph 2-30 I Me Me Cl 3,5-F₂—Ph In Table 2 X², R¹, R², Y² and Y⁴represent H, and A represents a nitrogen atom.

The endoparasite control agent of the present invention has excellentanti-endoparasite effect, and exerts appropriate control effect againstendoparasites. The animal for which the endoparasite control agent ofthe present invention can be used is a human and an animal of non-humanmammalian or avian species. Exemplary members of the non-human mammalianspecies include domestic animals, such as pigs, horses, cattle, sheep,goats, rabbits, camels, water buffalos, deer, mink and chinchillas; petanimals, such as dogs, cats, little birds and monkeys; and experimentalanimals, such as rats, mice, golden hamsters and guinea pigs. Exemplarymembers of the avian species include domestic fowls, such as chickens,ducks, aigamo ducks (crossbreeds of wild and domestic ducks), quails,domestic ducks, geese and turkeys. The examples listed above arenon-limiting examples.

Human endoparasites against which the endoparasite control agent of thepresent invention is effective are roughly classified into protozoa andhelminths. Examples of the protozoa include, but are not limitedthereto, Rhizopoda, such as Entamoeba histolytica; Mastigophora, such asLeishmania, Trypanosoma and Trichomonas; Sporozoea, such as Plasmodiumand Toxoplasma; and Ciliophora, such as Balantidium coli. Examples ofthe helminths include, but are not limited thereto, Nematoda, such asAscaris lumbricoides, Anisakis, Toxocara canis, Trichostrongylus spp.,Enterobius vemicularis, hookworms (for example, Ancylostoma duodenale,Necator americanus, Ancylostoma braziliense, etc.), Angiostrongylusspp., Gnathostoma spp., filarial worms (filaria, Wuchereria bancrofti,Brugia malayi, etc.), Onchocerca volvulus, Dracunculus medinensis,Trichinella spiralis and Strongyloides stercoralis; Acanthocephala, suchas Macracanthorhynchus hirudinaceus; Gordiacea, such as Gordioidea;Hirudinea, such as Hirudo nipponia; Trematoda, such as Schistosomajaponicum, Schistosoma mansoni, Schistosoma haematobium, Clonorchissinensis, Heterophyes heterophyes, Fasciola spp. and Paragonimus spp.;and Cestoda, such as Diphyllobothrium latum, Sparganum mansoni,Sparganum proliferum, Diplogonoporus grandis, Taeniidae for example,Taeniarhynchus saginatus, Taenia solium, Echinococcus, etc.),Hymenolepis spp., Dipylidium caninum, Mesocestoides lineatus, Bertiellaspp. and Nybelinia surmenicola.

Non-human mammalian or avian endoparasites against which theendoparasite control agent of the present invention is effective areroughly classified into protozoa and helminths. Examples of the protozoainclude, hut are not limited thereto, Apicomplexa, such as Cocoidia (forexample, Eimeria, Isospora, Toxoplasma, Neospora, Sarcocystis,Besnoitia, Hammondia, Cryptosporidium, Caryospora, etc.), Haemosporina(for example, Leucocytozoon, Plasmodium, etc.), Piroplasma (for example,Theileria, Anaplasma, Eperythrozoon, Haemobartonella, Ehrlichia, etc.),and others (for example, Hepatozoon, Haemogregarina, etc.); Microspora,such as Encephalitozoon and Nosema; Mastigophora, such as Trypanosomatid(for example, Trypanosoma, Leishmania, etc.), Trichomonadida (forexample, Chilomastix, Trichomonas, Monocercomonas, Histomonas, etc.),and Diplomonadida (for example, Hexamita, Giardia, etc.); Sarcodina,such as Amoebida (for example, Entamoeba histolytica (Entamoeba) etc.);and Ciliophora, such as Balantidium coli (Balantidium), Buxtonella andEntodinium.

Examples of the helminths include, but are not limited thereto,Nentatoda, such as Ascaridida (for example, Ascaris suum (Ascaris),Toxocara canis and Toxocara cati (Toxocara), Toxascaris leonina(Toxascaris), Parascaris equorum (Parascaris), Ascaridia galli(Ascaridia), Heterakis gallinarum (Heterakis), Anisakis, etc.), Oxyurida(for example, Oxyuris equi (Qxyuris), Passalurus ambiguus (Passalurus,etc.), Strongylida (for example, Strongylus vulgaris (Strongylus),Haemonchus contortus (Haemonchus), Ostertagia ostertagi (Ostertagia),Trichostrongylus colubriformis (Trichostrongylus), Cooperia punctata(Cooperia), Nematodirus filicollis (Nematodirus),Hyostrongylus rubidus(Hyostrongylus), Oesophagostomum radiatum (Oesophagostomum) Chabertiaovina (Chabertia), Ancylostoma caninum (Ancylostoma), Uncinariastenocephala (Uncinaria), Necator americanus (Necator), Bunostomumphlebotomum (Bunostomum), Dictyocaulus viviparus (Dictyocaulas),Metastrongylus elongatus (Metastrongylus), Filaroides hirthi(Filaroides), Aelurostrongylus abstrusus (Aelurostrongylus),Angiostrongylus cantonensis (Angiostrongylus), Syngamus trachea(Syngamus), Stephanurus dentatus (Stephanurus), etc.), Rhabditida (forexample, Strongyloides stercoralis (Strongyloides), Micronema, etc.),Spirurida (for example, Thelazia rhodesi (Thelazia), Oxyspirura mansoni(Oxyspirura), Spirocerca lupi (Spirocerca), Gongylonema pulchrum(Gongylonema), Draschia megastoma (Draschia), Habronema microstoma(Habronema), Ascarops strongylina(Ascarops), Physaloptera praeputialis(Physaloptera), Gnathostoma spinigerm (Gnathostoma), etc.), Filariida(for example, Dirofilaria immitis (Dirofilaria) Setaria equina(Setaria), Dipetalonema, Parafilaria multipapillosa (Parafilaria),Onchocerca cervicalis (Onchocerca), etc.), and Enoplida (for example,Parafilaria bovicola (Parafilaria), Stephanofilaria okinawaensis(Stephanofilaria), Trichuris vulpis (Trichuris), Capillaria bovis(Capillaria) Trichosomoides crassicauda (Trichosomoides), Trichinellaspiralis (Trichinella), Dioctophyma renale (Dioctophyma), etc.);Trematoda, such as Fasciolata (for example, Fasciola hepatica(Fasciola), Fasciolopsis buski (Fasciolopsis), etc.), Paramphistomatidae(for example, Homalogaster paloniae (Homalogaster), etc.), Dicrocoelata(for example, Eurytrema pancreaticum (Eurytrema), Dicrocoeliumdendriticum (Dicrocoelium), etc.), Diplostomata (for example,Pharyngostomum cordatum (Pharyngostomum), Alaria, etc.), Echinostomata(for example, Echinostoma hortense (Echinostoma), Echinochasmus, etc.),Troglotrematoidea (for example, lung flukes (Paragonimus), Nanophyetussalmincola (Nanophyetus), etc.), Opisthorchiida (for example, Clonorchissinensis (Clonorchis) etc.), Heterophyida (for example, Heterophyesheterophyes (Heterophyes), Metagonimus yokogawai (Metagonimus), etc.),Plagiorchiida (for example, Prosthogonimus ovatus (Prosthogonimus)etc.), and Schistosomatidae (for example, Schistosoma japonicum(Schistosoma) etc.); Cestoda, such as Pseudophylidea (for example,Diphyllobothrium nihonkaiense (Diphyllobothrium), Spirometra erinacei(Spirometra), etc.), and Cyclophyilldea (for example, Anoplocephalaperfoliata (Anoplocephala), Paranoplocephala mamillana(Paranoplocephala), Moniezia benedeni (Moniezia), Dipylidium caninum(Dipylidium), Mesocestoides lineatus (Mesocestoides), Taenia pisiformisand Taenia hydatigena (Taenia), Hydatigera taeniaeformis (Hydatigera),Multiceps multiceps (Multiceps), Echinococcus granulosus (Echinococcus),Echinococcus multilocularis (Echinococcus), Taenia solium (Taenia),Taeniarhynchus saginatus (Taeniarhynchus), Hymenolepis diminuta(Hymenolepis), Vampirolepis nana (Vampirolepis), Raillietina tetragona(Raillietina), Amoebotaenia sphenoides (Amoebotaenia), etc,);Acanthocephala, such as Macracanthorhynchus hirudinaceus(Macracanthorhynchus) and Moniliformis moniliformis (Moniliformis);Linguatulida, such as Linguatula serrata (Linguatula); and other variousparasites.

In different designations, examples of the helminths include, but arenot limited to, Nematoda, such as Enoplida (for example, Trichuris spp.,Capillaria spp., Trichomosoides spp., Trichinella spp., etc.), Rhabditia(for example, Micronema spp., Strongyloides spp., etc.), Strongylida(for example, Strongylus spp., Triodontophorus spp., Oesophagodontusspp., Trichonema spp., Gyalocephalus spp., Cylindropharynx spp.,Poteriostomum spp., Cyclococercus spp., Cylicostephanus spp.,Oesophagostomum spp., Chabertia spp., Stephanurus spp., Ancylostomaspp., Uncinaria spp., Bunostomum spp., Globocephalus spp., Syngamusspp., Cyathostoma spp., Metastrongylus spp., Dictyocaulus spp.,Muellerius spp., Protostrongylus spp., Neostrongylus spp., Cystocaulusspp., Pneumostrongylus spp., Spicocaulus spp., Elaphostrongylus spp.,Parelaphostrongylus spp., Crenosoma spp., Paracrenosoma spp.,Angiostrongylus spp., Aelurostrongylus spp., Filaroides, spp.,Parafilaroides spp., Trichostrongylus spp., Haemonchus spp., Ostertagiaspp., Marshallagia spp., Cooperia spp., Nematodirus spp., Hyostrongylusspp., Obelisoides spp., Amidostomum spp., Ollulanus spp., etc.),Oxyurida (for example, Oxyuris spp., Enterobius spp., Passalurus spp.,Syphacia spp., Aspiculuris spp., Heterakis spp., etc.), Ascaridia (forexample, Ascaris spp., Toxascaris spp., Toxocara spp., Parascaris spp.,Anisakis spp., Ascaridia spp., etc.), Spirurida (for example,Gnathostoma spp., Pyysaloptera spp., Thelazia spp., Gongylonema spp.,Habronema spp., Parabronema spp., Draschia spp., Dracunculus spp.,etc.), and Filariida (for example, Stephanofilaria spp., Parafilariaspp., Setaria spp., Loa spp., Dirofilaria spp., Litomosoides spp.,Brugia spp., Wuchereria spp., Onchocerca spp., etc.); Acanthocephala(for example, Filicollis spp.. Moniliformis spp., Macracanthorhynchusspp., Prosthenorchis spp., etc.); Trematoda including subclasses, suchas Monogenea (for example, Gyrodactylus spp., Dactylogyrus spp.,Polystoma spp., etc.) and Digenea (for example, Diplostomum spp.,Posthodiplostomum spp., Schistosoma spp., Trichobilharzia spp.,Ornithbilharzia spp., Austrobilharzia spp., Gigantobilharzia spp.,Leucochloridium spp., Brachylaima spp., Echinostoma spp.,Echinoparyphium spp., Echinochasmus spp., Hypoderaeum spp., Fasciolaspp., Fasciolides spp., Fasciolopsis spp., Cyclocoelum spp.,Typhlocoelum spp., Paramphistomum spp., Calicophoron spp., Cotylophoronspp., Gigantcotyle spp., Fischoederius spp., Gastrothylacus spp.,Notocotylus spp., Catatropis spp., Plagiorchis spp., Prosthogonimusspp., Dicrocoelium spp., Eurytrema spp., Troglatrema spp., Paragonimusspp., Collyriclum spp., Nanophyetus spp., Opisthorchis spp., Clonorchisspp., Metorchis spp., Heterophyes spp., Metagonimus spp., etc.);

Cestoda, such as Pseudophyllidea (for example, Diphyllobothrium spp.,Spirometra spp., Schistocephalus spp., Ligula spp., Bothridium spp.,Diplogonoporus spp., etc.), and Cyclophyllidea (for example,Mesocestoides spp., Anoplocephala spp., Paranoplocehala spp., Monieziaspp., Thysanosomsa spp., Thysaniezia spp., Avitellina spp., Stilesiaspp., Cittotaenia spp., Andyra spp., Bertiella spp., Taenia spp.,Echinococcus spp., Hydatigera spp., Davainea spp., Raillietina spp.,Hymenolepis spp., Echinolepis spp., Echinocotyle spp., Diorchis spp.,Dipylidium spp., Joyeuxiella spp., Diplopylidium spp., etc.); and othersincluding parasites belonging to Acanthocephala and Linguatulida.

The endoparasite control agent of the present invention is effective forcontrolling not only parasites that live in the body of an intermediateor final host, but also parasites that live in the body of a reservoirhost. The compound represented by the general formula (I) of the presentinvention is effective for controlling parasites at their everydevelopmental stage. For example, in the case of protozoa, the compoundis effective against their cysts, precystic forms and trophozoites;schizonts and amoeboid forms at the asexual stage; gametocytes, gametesand zygotes at the sexual stage; sporozoites; etc. In the case ofnematodes, the compound is effective against their eggs, larvae andadults. The compound of the present invention is capable of not onlydisinfecting parasites in the living body, but also even preventingparasitic infection by application to the environment as a route ofinfection. For example, soil-borne infection, i.e., infection from soilof crop fields and parks; percutaneous infection from water in rivers,lakes, marshes, paddy fields, etc.; oral infection from feces of animalssuch as dogs and cats; oral infection from saltwater fish, freshwaterfish, crustaceans, shellfish, raw meat of domestic animals, etc.;infection from mosquitoes, gadflies, flies, cockroaches, mites andticks, fleas, lice, assassin bugs, trombiculid mites, etc.; and the likecan be prevented from occurring.

The endoparasite control agent of the present invention can beadministered as a pharmaceutical for treatment or prevention ofparasitosis in humans and animals of non-human mammalian or avianspecies. The mode of administration may be oral or parenteraladministration. In the case of oral administration, the endoparasitecontrol agent of the present invention can be administered, for example,as a capsule, a tablet, a pill, a powder, a granule, a fine granule, apowder, a syrup, an enteric-coated preparation, a suspension or a paste,or after blended in a liquid drink or feed for animals. In the case ofparenteral administration, the endoparasite control agent of the presentinvention can be administored, for example, as an injection, aninfusion, a suppository, an emulsion, a suspension, a drop, an ointment,a cream, a solution, a lotion, a spray, an aerosol, a cataplasm or atape, or in a dosage form which allows sustained mucosal or percutaneousabsorption.

In the case where the endoparasite control agent of the presentinvention is used as a pharmaceutical for humans and animals ofnon-human mammalian or avian species, the optimum amount (effectiveamount) of the active ingredient varies with the purpose (treatment orprevention), the kind of infectious parasite, the type and severity ofinfection, the dosage form, etc., but in general, the oral daily dose isin the range of about 0.0001 to 10000 mg/kg body weight and theparenteral daily dose is in the range of about 0.0001 to 10000 mg/kgbody weight. Such a dose may be given as a single dose or divided intomultiple doses.

The concentration of the active ingredient in the endoparasite controlagent of the present invention is generally about 0.001 to 100% by mass,preferably about 0.001 to 99% by mass, and more preferably about 0.005to 20% by mass. The endoparasite control agent of the present inventionmay be a composition that can be directly administered, or a highlyconcentrated composition that needs to be diluted to a suitableconcentration before use.

The endoparasite control agent of the present invention can be used incombination with any existing endoparasite control agent for the purposeof reinforcing or complementing its effect. In such a combined use, twoor more active ingredients may be mixed and formulated into a singlepreparation before administration, or two or more different preparationsmay be administered separately.

EXAMPLES

Next, the present invention will be illustrated in detail by formulationexamples and test example of the endoparasite control agent of thepresent invention, but the scope of the present invention is not limitedby the following formulation examples and test example.

In Examples, “part” means a part by mass.

Formulation Example 1 Emulsion

Ten parts of a carboxamide derivative represented by the general formula(I) of the present invention, 6 parts of Sorpol 355S (surfactant,manufactured by Toho Chemical Industry), and 84 parts of Solvesso 150(manufactured by Exxon) are uniformly mixed with stirring to give anemulsion.

Formulation Example 2 Ointment

One part of a carboxamide derivative represented by the general formula(I) of the present invention, 50 parts of white beeswax, and 43 parts ofwhite petrolatum are well mixed to give an ointment.

Formulation Example 3 Tablet

Two parts of a carboxamide derivative represented by the general formula(I) of the present invention, 10 parts of vegetable oil (olive oil), 3parts of crystalline cellulose, 20 parts of white carbon, and 65 partsof kaolin are well mixed and compressed into a tablet.

Formulation Example 4 Injection

Ten parts of a carboxamide derivative represented by the general formula(I) of the present invention, 10 parts of propylene glycol for use as afood additive, and 80 parts of vegetable oil (corn oil) are mixed togive an injection.

Formulation Example 5 Solution

Five parts of a carboxamide derivative represented by the generalformula (I) of the present invention, 20 parts of a surfactant forordinary use as a dissolution or suspension aid, and 75 parts of ionexchanged water are well mixed to give a solution.

Test Example Test for Effect on Motion of Larvae of Haemonchus Nematode(Haemonchus contortus)

The compound of the present invention was prepared as solutions in 100%DMSO at the final concentrations of 50 ppm, 5 ppm, 0.5 ppm, 0.05 ppm and0.005ppm. DMSO stands for dimethyl sulfoxide.

A larval suspension containing 1st-stage larvae of Haemonchus contortusharvested by the Baermann technique (for example, see K. Nakazono etal., “Inclination of Baermann funnel wall and efficiency of nematodeextraction” Proc. Assoc. Pl. Prot. Kyushu 33: 126-130 (1987)) was placedat a density of 20 larvae per well in a test plate, and 0.5 μL/well ofthe test solution containing the compound of the present inventiondiluted to a predetermined concentration was added to the test plate.The plate was kept under the conditions of 27° C./95% RH for 4 days. Inthe test, ivermectin was used for the positive control and DMSO was usedfor the negative control.

The motor ability of the larvae was examined with an automatic analyzerequipped with an LCD camera. The inhibitory effect on the motion of thelarvae in each treatment plot was corrected based on the inhibitoryeffect in the plot treated with DMSO only for the negative control. TheEC₅₀ value was calculated from the data on the corrected inhibitoryeffect on the motion of the larvae, and graded according to the criteriashown below.

The test was conducted in duplicate per plot.

Grading Criteria

EC₅₀ value:

0.05 ppm or less A 0.05 to 1 ppm B 1 to 10 ppm C 10 ppm or more D

As a result, the compounds 1-1, 1-2, 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9,1-10, 1-11, 1-13, 1-14, 1-15, 1-16, 1-17, 1-18, 1-19, 1-20, 1-21, 1-22,1-23, 1-24, 1-25, 1-26, 1-27, 1-28, 1-29, 1-30, 1-31, 1-32, 1-34, 1-35,1-36, 1-37, 1-38, 1-39, 1-40, 1-41, 1-42, 1-43, 1-44, 1-45, 1-45, 1-47,1-48, 1-49, 1-50, 1-51, 1-52, 1-53, 1-54, 1-55, 1-56, 1-57,1-58, 1-59,1-60, 1-61, 1-62, 1-63, 1-64, 1-65, 1-66, 1-67, 2-1, 2-2, 2-3, 2-4 and2-5 of the present invention showed the activity level graded as C orhigher.

The results show that the compounds of the present invention areeffective as an endoparasite control agent.

1-11. (canceled)
 12. A method for controlling endoparasites, comprisingorally or parenterally administering, to a mammal or a bird, aneffective amount of an endoparasite control agent comprising, as anactive ingredient, a carboxamide derivative represented by the generalformula (I):

wherein A represents a nitrogen atom or a C—Y⁵ group (wherein Y⁵ is ahydrogen atom or a (C₁-C₆) alkyl group), X¹ and X² may be the same ordifferent, and each represent (a1) a hydrogen atom; (a2) a halogen atom;p0 (a3) a (C₁-C₆) alkyl group; (a4) a halo (C₁-C₆) alkyl group; (a5) a(C₁-C₆) alkoxy group; or (a6) a halo (C₁-C₆) alkoxy group, R¹ and R² maybe the same or different, and are selected from the group consisting of(b1) a hydrogen atom; (b2) a halogen atom; (b3) a (C₁-C₆) alkyl group;(b4) a (C₁-C₆) alkoxy group; and (b5) a halo (C₁-C₆) alkyl group, oroptionally (b6) R¹ and R² together with the carbon atom bound to R¹ andR² form a (C₃-C₆) cycloalkane, R³ and R⁴ may be the same or different,and are selected from the group consisting of (c1) a hydrogen atom; (c2)a halogen atom; (c3) a (C₁-C₆) alkyl group; (c4) a (C₁-C₆) alkoxy group;and (c5) a halo (C₁-C₆) alkyl group; or optionally (c6) R³ and R⁴together with the carbon atom bound to R³ and R⁴ form a (C₃-C₆)cycloalkane, Y¹ represents (d1) a hydrogen atom; (d2) a halogen atom;(d3) a (C₁-C₆) alkyl group; (d4) a halo (C₁-C₆) alkyl group; (d5) a(C₁-C₆) alkoxy group; or (d6) a halo (C₁-C₆) alkoxy group, Y² and Y⁴ maybe the same or different, and each represent (e1) a hydrogen atom; (e2)a halogen atom; (e3) a (C₁-C₆) alkyl group; (e4) a halo (C₁-C₆) alkylgroup; (e5) a (C₁-C₆) alkoxy group; or (e6) a halo (C₁-C₆) alkoxy group,and Y³ represents (f1) a phenyl group; (f2) a phenyl group having, onthe ring, 1 to 5 substituting groups which may be the same or differentand are selected from the group consisting of (a) a halogen atom, (b) acyano group, (c) a nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo(C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆)alkoxy group; (f3) a phenoxy group; (f4) a phenoxy group having, on thering, 1 to 5 substituting groups which may be the same or different andare selected from the group consisting of (a) a halogen atom, (b) acyano group, (c) a nitro group, (d) a (C₁-C₆) alkyl group, (f) a (C₁-C₆)alkoxy group and (g) a halo (C₁-C₆) alkoxy group; (f5) a pyridyl group;(f6) a pyridyl group having, on the ring, 1 to 4 substituting groupswhich may be the same or different and are selected from the groupconsisting of (a) a halogen atom, (b) a cyano group, (c) a nitro group,(d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl group, (f) a (C₁-C₆)alkoxy group and (g) a halo (C₁-C₆) alkoxy group; (f7) a pyridyloxygroup; (f8) a pyridyloxy group having, on the ring, 1 to 4 substitutinggroups which may be the same or different and are selected from thegroup consisting of (a) a halogen atom, (b) a cyano group, (c) a nitrogroup, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl group, (f) a(C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy group; (f9) apyrimidyloxy group; (f10) a pyrimidyloxy group having, on the ring, 1 to3 substituting groups which may be the same or different and areselected from the group consisting of (a) a halogen atom, (b) a cyanogroup, (c) a nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆)alkyl group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxygroup; (f11) a pyrazyloxy group; (f12) a pyrazyloxy group having, on thering, 1 to 3 substituting groups which may be the same or different andare selected from the group consisting of (a) a halogen atom, (b) acyano group, (c) a nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo(C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆)alkoxy group; (f13) a pyrazolyloxy group; (f14) a pyrazolyloxy grouphaving, on the ring, 1 to 3 substituting groups which may be the same ordifferent and are selected from the group consisting of (a) a halogenatom, (b) a cyano group, (c) a nitro group, (d) a (C₁-C₆) alkyl group,(e) a halo (C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group, (g) a halo(C₁-C₆) alkoxy group and (h) a formyl group; (f15) a quinolyloxy group;(f16) a quinolyloxy group having, on the ring, 1 to 6 substitutinggroups which may be the same or different and are selected from thegroup consisting of (a) a halogen atom, (b) a cyano group, (c) a nitrogroup, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl group, (f) a(C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy group; (f17) aquinoxalyloxy group; (f18) a quinoxalyloxy group having, on the ring, 1to 5 substituting groups which may be the same or different and areselected from the group consisting of (a) a halogen atom, (b) a cyanogroup, (c) a nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆)alkyl group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxygroup; (f19) a benzoxazolyloxy group; (f20) a benzoxazolyloxy grouphaving, on the ring, 1 to 4 substituting groups which may be the same ordifferent and are selected from the group consisting of (a) a halogenatom, (b) a cyano group, (c) a nitro group, (d) a (C₁-C₆) alkyl group,(e) a halo (C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g) ahalo (C₁-C₆) alkoxy group; (f21) a benzothiazolyloxy group; or (f22) abenzothiazolyloxy group having, on the ring, 1 to 4 substituting groupswhich may be the same or different and are selected from the groupconsisting of (a) a halogen atom, (b) a cyano group, (c) a nitro group,(d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkyl group, (f) a (C₁-C₆)alkoxy group and (g) a halo (C₁-C₆) alkoxy group}, or a salt thereof.13. The method according to claim 12, wherein the endoparasite controlagent is orally or parenterally administered to a non-human mammal. 14.The method according to claim 13, wherein the non-human mammal is adomestic animal.
 15. The method according to claim 12, wherein themammal is a human.
 16. The method according to claim 12, wherein themammal is a non-human mammal.
 17. The method according to claim 12,wherein A represents a nitrogen atom or a C—H group, X¹ and X² may bethe same or different, and each represent (a1) a hydrogen atom; (a2) ahalogen atom; or (a4) a halo (C₁-C₆) alkyl group, R¹ and R² eachrepresent (b1) a hydrogen atom, R³ and R⁴ may be the same or different,and are selected from the group consisting of (c1) a hydrogen atom; (c3)a (C₁-C₆) alkyl group; and (c4) a (C₁-C₆) alkoxy group, or optionally(c6) R³ and R⁴ together with the carbon atom bound to R³ and R⁴ form a(C₃-C₆) cycloalkane, Y¹ represents (d2) a halogen atom, Y² and Y⁴ eachrepresent (e1) a hydrogen atom, and Y³ is selected from the groupconsisting of (f1) a phenyl group; (f2) a phenyl group having, on thering, 1 to 5 substituting groups which may be the same or different andare selected from the group consisting of (a) a halogen atom, (b) acyano group, (c) a nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo(C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆)alkoxy group; (f3) a phenoxy group; (f4) a phenoxy group having, on thering, 1 to 5 substituting groups which may be the same or different andare selected from the group consisting of (a) a halogen atom, (b) acyano group, (c) a nitro group, (d) a (C₁-C₆) alkyl group, (f) a (C₁-C₆)alkoxy group and (g) a halo (C₁-C₆) alkoxy group; (f5) a pyridyl group;(f7) a pyridyloxy group; (f8) a pyridyloxy group having, on the ring, 1to 4 substituting groups which may be the same or different and areselected from the group consisting of (a) a halogen atom, (b) a cyanogroup, (c) a nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆)alkyl group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxygroup; (f10) a pyrimidyloxy group having, on the ring, 1 to 3substituting groups which may be the same or different and are selectedfrom the group consisting of (a) a halogen atom, (b) a cyano group, (c)a nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkylgroup, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy group;(f11) a pyrazyioxy group; (f12) a pyrazyloxy group having, on the ring,1 to 3 substituting groups which may be the same or different and areselected from the group consisting of (a) a halogen atom, (b) a cyanogroup, (c) a nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆)alkyl group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxygroup; (f14) a pyrazolyloxy group having, on the ring, 1 to 3substituting groups which may be the same or different and are selectedfrom the group consisting of (a) a halogen atom, (b) a cyano group, (c)a nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkylgroup, (f) a (C₁-C₆) alkoxy group, (g) a halo (C₁-C₆) alkoxy group and(h) a formyl group; (f15) a quinolyloxy group; (f17) a quinoxalyloxygroup; (f19) a benzoxazolyloxy group; (f21) a benzothiazolyloxy group;and (f22) a benzothiazolyloxy group having, on the ring, 1 to 4substituting groups which may be the same or different and are selectedfrom the group consisting of (a) a halogen atom, (b) a cyano group, (c)a nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo (C₁-C₆) alkylgroup, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxy group.18. The method according to claim 12, wherein A represents a C—H group,X¹ and X² may be the same or different, and are selected from the groupconsisting of (a1) a hydrogen atom; (a2) a halogen atom; and (a4) a halo(C₁-C₆) alkyl group, R¹ and R² each represent (b1) a hydrogen atom, R³and R⁴ may be the same or different, and are selected from the groupconsisting of (c1) a hydrogen atom; (c3) a (C₁-C₆) alkyl group; and (c4)a (C₁-C₆) alkoxy group, or optionally (c6) R³ and R⁴ together with thecarbon atom bound to R³ and R⁴ form a (C₃-C₆) cycloalkane, Y¹ represents(d2) a halogen atom, Y² and Y⁴ each represent (e1) a hydrogen atom, andY³ is selected from the group consisting of (f1) a phenyl group; (f2) aphenyl group having, on the ring, 1 to 5 substituting groups which maybe the same or different and are selected from the group consisting of(a) a halogen atom, (b) a cyano group, (c) a nitro group, (d) a (C₁-C₆)alkyl group, (e) a halo (C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy groupand (g) a halo (C₁-C₆) alkoxy group; (f3) a phenoxy group; (f4) aphenoxy group having, on the ring, 1 to 5 substituting groups which maybe the same or different and are selected from the group consisting of(a) a halogen atom, (b) a cyano group, (c) a nitro group, (d) a (C₁-C₆)alkyl group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxygroup; (f5) a pyridyl group; (f7) a pyridyloxy group; (f8) a pyridyloxygroup having, on the ring, 1 to 4 substituting groups which may be thesame or different and are selected from the group consisting of (a) ahalogen atom, (b) a cyano group, (c) a nitro group, (d) a (C₁-C₆) alkylgroup, (e) a halo (C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and(g) a halo (C₁-C₆) alkoxy group; (f10) a pyrimidyloxy group having, onthe ring, 1 to 3 substituting groups which may be the same or differentand are selected from the group consisting of (a) a halogen atom, (b) acyano group, (c) a nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo(C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆)alkoxy group; (f11) a pyrazyloxy group; (f12) a pyrazyloxy group having,on the ring, 1 to 3 substituting groups which may be the same ordifferent and are selected from the group consisting of (a) a halogenatom, (b) a cyano group, (c) a nitro group, (d) a (C₁-C₆) alkyl group,(e) a halo (C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g) ahalo (C₁-C₆) alkoxy group; (f14) a pyrazolyloxy group having, on thering, 1 to 3 substituting groups which may be the same or different andare selected from the group consisting of (a) a halogen atom, (b) acyano group, (c) a nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo(C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group, (g) a halo (C₁-C₆)alkoxy group and (h) a formyl group; (f15) a quinolyloxy group; (f17) aquinoxalyloxy group; (f19) a benzoxazolyloxy group; (f21) abenzothiazolyloxy group; and (f22) a benzothiazolyloxy group having, onthe ring, 1 to 4 substituting groups which may be the same or differentand are selected from the group consisting of (a) a halogen atom, (b) acyano group, (c) a nitro group, (d) a (C₁-C₆) alkyl group, (e) a halo(C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆)alkoxy group.
 19. The method according to claim 12, wherein A representsa nitrogen atom, X¹ and X² may be the same or different, and areselected from the group consisting of (a1) a hydrogen atom; (a2) ahalogen atom; and (a4) a halo (C₁-C₆) alkyl group, R¹ and R² eachrepresent (b1) a hydrogen atom, R³ and R⁴ may be the same or different,and are selected from the group consisting of (c1) a hydrogen atom; and(c3) a (C₁-C₆) alkyl group, Y¹ represents (d2) a halogen atom; or (d3) a(C₁-C₆) alkyl group, Y² and Y⁴ each represent (e1) a hydrogen atom, andY³ is selected from the group consisting of (f1) a phenyl group; (f2) aphenyl group having, on the ring, 1 to 5 substituting groups which maybe the same or different and are selected from the group consisting of(a) a halogen atom, (b) a cyano group, (c) a nitro group, (d) a (C₁-C₆)alkyl group, (e) a halo (C₁-C₆) alkyl group, (f) a (C₁-C₆) alkoxy groupand (g) a halo (C₁-C₆) alkoxy group; (f3) a phenoxy group; (f4) aphenoxy group having, on the ring, 1 to 5 substituting groups which maybe the same or different and are selected from the group consisting of(a) a halogen atom, (b) a cyano group, (c) a nitro group, (d) a (C₁-C₆)alkyl group, (f) a (C₁-C₆) alkoxy group and (g) a halo (C₁-C₆) alkoxygroup; and (f5) a pyridyl group.